{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T13:23:29Z","timestamp":1782221009922,"version":"3.54.5"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Nephrol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Proteinuria is a prevalent symptom of pediatric nephrology, while kidney biopsy remains the gold standard for kidney tissue analysis, and it is currently controversial. We report the rare case that the mutation in the AMN gene was considered to cause chronically isolated proteinuria and also suggest that renal biopsy should be chosen with caution in children with chronic isolated non-nephrotic levels of proteinuria and that genetic testing may be feasible for the early precise diagnosis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>A 35-month-old boy presented with excessive urine foaming for more than half a month; his proteinuria was considered non-nephrotic range and urine protein electrophoresis was suggestive of mixed proteinuria; other than that, the investigations are non-specific. Given the child\u2019s chronic isolated proteinuria and good renal function, we chose to refine the genetic test rather than a renal biopsy; a compound heterozygous variant was found in the AMN gene of this child which was caused by a point mutation in the father, and a partial chromosomal deletion in the mother.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Cubilin(encoded by CUBN), amnionless(encoded by AMN), and megalin form a multiligand receptor complex; CUBN or AMN gene variants have been implicated as a hereditary cause of megaloblastic anemia, proteinuria, and neurological impairment. In the past few decades, chronic isolated proteinuria caused by CUBN gene variants is benign, non-progressive, and has normal renal function. However, the child is the first reported case of isolated proteinuria of AMN gene mutation, indicating that the earlier diagnostic genetic sequencing in an otherwise well, not nephrotic proteinuria child may be a convenient, cost-effective, and harmless option, challenging the traditional paradigm.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12882-024-03660-5","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T11:03:07Z","timestamp":1720695787000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Controversy between biopsy and risk in children with proteinuria: is there a paradigm war?"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3307-0158","authenticated-orcid":false,"given":"Jingyi","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"issue":"1","key":"3660_CR1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1159\/000168199","volume":"10","author":"S Cameron","year":"1990","unstructured":"Cameron S. 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Written informed assent was obtained from a parent or legal guardian for participants under 18 years old. All procedures performed in our studies were in accordance with these ethical standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"We obtained written informed consent for publication of the article, including any identifiable data and images from the parents of the minor. Written informed consent for publication of his clinical details and\/or clinical images was obtained from the patient\u2014a copy of the consent form is available for review by the Editor of this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"221"}}